Crystal structures reveal the molecular basis of ion translocation in sodium/proton antiporters. 2016

Mathieu Coincon, and Povilas Uzdavinys, and Emmanuel Nji, and David L Dotson, and Iven Winkelmann, and Saba Abdul-Hussein, and Alexander D Cameron, and Oliver Beckstein, and David Drew
Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.

To fully understand the transport mechanism of Na(+)/H(+) exchangers, it is necessary to clearly establish the global rearrangements required to facilitate ion translocation. Currently, two different transport models have been proposed. Some reports have suggested that structural isomerization is achieved through large elevator-like rearrangements similar to those seen in the structurally unrelated sodium-coupled glutamate-transporter homolog GltPh. Others have proposed that only small domain movements are required for ion exchange, and a conventional rocking-bundle model has been proposed instead. Here, to resolve these differences, we report atomic-resolution structures of the same Na(+)/H(+) antiporter (NapA from Thermus thermophilus) in both outward- and inward-facing conformations. These data combined with cross-linking, molecular dynamics simulations and isothermal calorimetry suggest that Na(+)/H(+) antiporters provide alternating access to the ion-binding site by using elevator-like structural transitions.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D002151 Calorimetry The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D016963 Thermus thermophilus A species of gram-negative, aerobic, rod-shaped bacteria found in hot springs of neutral to alkaline pH, as well as in hot-water heaters.
D056004 Molecular Dynamics Simulation A computer simulation developed to study the motion of molecules over a period of time. Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics
D017923 Sodium-Hydrogen Exchangers A family of plasma membrane exchange glycoprotein antiporters that transport sodium ions and protons across lipid bilayers. They have critical functions in intracellular pH regulation, cell volume regulation, and cellular response to many different hormones and mitogens. Na(+)-H(+)-Antiporter,Na(+)-H(+)-Exchanger,Sodium-Hydrogen Antiporter,Na(+)-H(+)-Antiporters,Na(+)-H(+)-Exchangers,SLC9 Na(+)-H(+) Exchangers,SLC9 Protein Family,SLC9 Proteins,SLC9-NHE Protein Family,Sodium-Hydrogen Antiporters,Sodium-Hydrogen Exchanger,Sodium-Proton Antiporter,Sodium-Proton Antiporters,Solute Carrier 9 Protein Family,Solute Carrier 9 Proteins,Antiporter, Sodium-Hydrogen,Antiporter, Sodium-Proton,Antiporters, Sodium-Hydrogen,Antiporters, Sodium-Proton,Exchanger, Sodium-Hydrogen,Exchangers, Sodium-Hydrogen,Protein Family, SLC9,Protein Family, SLC9-NHE,SLC9 NHE Protein Family,Sodium Hydrogen Antiporter,Sodium Hydrogen Antiporters,Sodium Hydrogen Exchanger,Sodium Hydrogen Exchangers,Sodium Proton Antiporter,Sodium Proton Antiporters
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies

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